Journal
CELL REPORTS
Volume 20, Issue 13, Pages 3223-3235Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2017.09.007
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Funding
- NSF [DMS-1463137, DMS-1418172]
- NIH [GM084905]
- DARPA [WF911NF-14-1-0395]
- NSF of China [31500676]
- Anhui Province [1508085SQC202]
- Division Of Mathematical Sciences
- Direct For Mathematical & Physical Scien [1462049] Funding Source: National Science Foundation
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Quiescence is a non-proliferative cellular state that is critical to tissue repair and regeneration. Although often described as the G0 phase, quiescence is not a single homogeneous state. As cells remain quiescent for longer durations, they move progressively deeper and display a reduced sensitivity to growth signals. Deep quiescent cells, unlike senescent cells, can still re-enter the cell cycle under physiological conditions. Mechanisms controlling quiescence depth are poorly understood, representing a currently underappreciated layer of complexity in growth control. Here, we show that the activation threshold of a Retinoblastoma (Rb)-E2F network switch controls quiescence depth. Particularly, deeper quiescent cells feature a higher E2F-switching threshold and exhibit a delayed traverse through the restriction point (R-point). We further show that different components of the Rb-E2F network can be experimentally perturbed, following computer model predictions, to coarse-or fine-tune the E2F-switching threshold and drive cells into varying quiescence depths.
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